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Purpose: Intravenous ketamine is often prescribed in severe neuropathic pain. Oral -methyl-D-aspartate receptor (NMDAR) antagonists might prolong pain relief, reducing the frequency of ketamine infusions and hospital admissions. This clinical trial aimed at assessing whether oral dextromethorphan or memantine might prolong pain relief after intravenous ketamine.
Patients And Methods: A multicenter randomized controlled clinical trial included 60 patients after ketamine infusion for refractory neuropathic pain. Dextromethorphan (90 mg/day), memantine (20 mg/day) or placebo was given for 12 weeks (n=20 each) after ketamine infusion. The primary endpoint was pain intensity at one month. Secondary endpoints included pain, sleep, anxiety, depression, cognitive function and quality of life evaluations up to 12 weeks.
Results: At 1 month, dextromethorphan maintained ketamine pain relief (Numeric Pain Scale: 4.01±1.87 to 4.05±2.61, =0.53) and diminished pain paroxysms (=0.03) while pain intensity increased significantly with memantine and placebo (=0.04). At 3 months, pain remained lower than at inclusion (=0.001) and was not significantly different in the three groups. Significant benefits were observed on cognitive-affective domains and quality of life for dextromethorphan and memantine (<0.05).
Conclusions: Oral dextromethorphan given after ketamine infusion extends pain relief during one month and could help patients to better cope with pain. Future studies should include larger populations stratified on pharmacogenetics screening. Optimization of an oral drug that could extend ketamine antihyperalgesia, with fewer hospital admissions, remains a prime challenge in refractory neuropathic pain.
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http://dx.doi.org/10.2147/DDDT.S207350 | DOI Listing |
Cochrane Database Syst Rev
August 2025
School of Health Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia.
Rationale: N-methyl-D-aspartate (NMDA) receptor antagonists are a group of medicines classed according to their mechanism of action. Ketamine and other NMDA receptor antagonists are used to treat chronic pain, despite uncertain benefits and harms.
Objectives: To evaluate the benefits and harms of ketamine and other NDMA receptor antagonists compared to placebo, usual care, or other medicines for adults with chronic non-cancer, non-headache pain.
Beijing Da Xue Xue Bao Yi Xue Ban
August 2025
Department of Toxicology, Peking University School of Public Health, Key Laboratory of State Administration of Traditional Chinese Medicine for Compatibility Toxicology, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China.
Objective: To investigate whether escin (ESC) and dextromethorphan (DEX) have the protective effects on the progression and symptoms of Alzheimer disease (AD).
Methods: The AD model of () was established by transgenic amyloid β-protein (Aβ protein). Different concentrations of ESC or DEX or 50 μmol/L memantine (MEM) were used to treat the AD model worms, and their lifespan was detected.
Expert Rev Neurother
August 2025
Division of Neurosurgery, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
Introduction: Traumatic brain injury (TBI) is a leading cause of long-term disability. N-methyl-D-aspartate receptor (NMDAR) signaling constitutes an important target for pharmacological treatment options.
Methods: The authors have systematically reviewed primary clinical literature reporting on FDA-approved NMDAR antagonist treatment in TBI, based on a set of pre-defined eligibility criteria.
Int J Mol Sci
October 2024
Faculty of Pharmacy, "Ovidius" University of Constanța, Căpitan Aviator Al. Şerbănescu 6, 900470 Constanța, Romania.
Neuropathic pain (NeP) is a complex and debilitating condition that impacts millions of people globally. Although various treatment options exist, their effectiveness is often limited, and they can be accompanied by significant side effects. In recent years, there has been increasing interest in targeting the N-methyl-D-aspartate receptor (NMDAR) as a potential therapeutic approach to alleviate different types of neuropathic pain.
View Article and Find Full Text PDFPsychopharmacol Bull
July 2024
Dr. Schatzberg is Kenneth T. Norris, Jr. professor in the Department of Psychiatry and Behavioral Sciences at the Stanford University School of Medicine in California.